This proposal seeks to establish a Specialized Center of Interdisciplinary Research (SCOR) on the overarching theme of sex and gender factors affecting addiction and health. The Center's mission is to address the health concerns of women and their developing offspring affected by drug abuse by providing the optimal environment to encourage and facilitate clinical and translational research. The approach will be to use interdisciplinary translational and clinical studies to assess sex/gender-specific differences in vulnerability to drug-taking and drug effects across development in adolescent and adult females and males with and without prenatal exposure to cocaine and other drugs. Project #1 (PI: Dow-Edwards), "Sex Differences in Drug Effects: The Prenatal Trajectory", is a series of preclinical translational studies using an established rat model of prenatal drug exposure. This project will examine the roles of prenatal cocaine exposure, postnatal environment, and polydrug exposure (cocaine with nicotine, THC, and alcohol) in the development of drug-taking behavior in male and female adolescent rats, emphasizing sex differences in conditioned place preference for cocaine and elucidating the potential biologic basis for sex differences by functional imaging and neurochemical assessments. Project #2 (PI: Izenwasser), "Sex Differences in Drug Effects: The Adolescent Trajectory" is a series of preclinical translational studies, the focus of which is to study the effects of nicotine, marijuana (A9-THC) and cocaine in male and female adolescent and adult rats on behavior and neurochemistry during adolescence and later during adulthood. Project #3 (PI: Bandstra), "Sex and Gender Influences on Adolescent Drug Involvement" is a clinical investigation of sex and gender differences affecting risk for drug abuse in adolescents (and ultimately as adults) with and without prenatal exposure to cocaine and other drugs. Subjects were enrolled in the Miami Prenatal Cocaine Study (n=476);and assessed through early adolescence (retention 85 percent) for neuropsychological and other outcomes. In this proposal, subjects will be assessed at age 16 and 18 years by self-report and biomarkers for drug involvement, caregiver and self-report of psychosocial risk factors, and laboratory measures of stress reactivity, risk-taking, and decision-making. Analyses will include consideration of the influence of prenatal cocaine exposure on later drug involvement in the female and male adolescents. The Administrative Core will host a Scientific Steering Committee and Internal and External Advisory Committees of interdisciplinary investigators with relevant expertise. Enhanced understanding of the differential effects of drugs of abuse in females and males across development (from prenatal to postnatal exposures during adolescence and adulthood) should lead to improved sex-, gender-, and age-specific preventions and treatments for drug addiction and related conditions.